Succar Rebecca, Mitchell Vanessa A, Vaughan Christopher W
Pain Management Research Institute, Northern Clinical School, The University of Sydney at Royal North Shore Hospital, St Leonards, 2065, NSW, Australia.
Mol Pain. 2007 Aug 30;3:24. doi: 10.1186/1744-8069-3-24.
While cannabinoid receptor agonists have analgesic activity in inflammatory pain states they produce a range of side effects. Recently, it has been demonstrated that the arachidonic acid-amino acid conjugate, N-arachidonyl-glycine (NA-glycine) is effective in acute pain models.
In the present study we examined the effect of NA-glycine in a rat model of inflammatory pain. Intrathecal administration of NA-glycine (70 - 700 nmol) and the pan-cannabinoid receptor agonist HU-210 (10 nmol) reduced the mechanical allodynia and thermal hyperalgesia induced by intraplantar injection of Freund's complete adjuvant (FCA). The actions of HU-210, but not NA-glycine were reduced by the cannabinoid CB1 receptor antagonist AM251. The cannabinoid CB2 receptor antagonist SR144528 also had no effect on the actions of NA-glycine. In contrast, N-arachidonyl-GABA (NA-GABA, 700 nmol) and N-arachidonyl-alanine (NA-alanine, 700 nmol) had no effect on allodynia and hyperalgesia. HU-210, but not NA-glycine produced a reduction in rotarod latency.
These findings suggest that NA-glycine may provide a novel non-cannabinoid receptor mediated approach to alleviate inflammatory pain.
虽然大麻素受体激动剂在炎症性疼痛状态下具有镇痛活性,但它们会产生一系列副作用。最近,已证明花生四烯酸 - 氨基酸共轭物N - 花生四烯酰甘氨酸(NA - 甘氨酸)在急性疼痛模型中有效。
在本研究中,我们研究了NA - 甘氨酸在大鼠炎症性疼痛模型中的作用。鞘内注射NA - 甘氨酸(70 - 700 nmol)和泛大麻素受体激动剂HU - 210(10 nmol)可减轻足底注射弗氏完全佐剂(FCA)诱导的机械性异常性疼痛和热痛觉过敏。大麻素CB1受体拮抗剂AM251可减弱HU - 210的作用,但对NA - 甘氨酸的作用无影响。大麻素CB2受体拮抗剂SR144528对NA - 甘氨酸的作用也无影响。相比之下,N - 花生四烯酰 - γ-氨基丁酸(NA - GABA,700 nmol)和N - 花生四烯酰丙氨酸(NA - 丙氨酸,700 nmol)对异常性疼痛和痛觉过敏无影响。HU - 210可缩短转棒试验潜伏期,但NA - 甘氨酸无此作用。
这些发现表明,NA - 甘氨酸可能提供一种新的非大麻素受体介导的方法来减轻炎症性疼痛。